Disrupting Biofilms and Enhancing Antibacterial Activity via Novel Ciprofloxacin-Lipid Conjugates

  • J Med Chem. 2026 May 14;69(9):10979-10992. doi: 10.1021/acs.jmedchem.6c00137.
Rahul Kumar  1  2 ,  Kishan Kumar Parida  3 ,  Aman Dalal  3 ,  Puja Kumari Agnivesh  3 ,  Ankit Saneja  2  4 ,  Nitin Pal Kalia  3 ,  Sushil K Maurya  1  2
Affiliations
  • 1. Chemical Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176 061, India.
  • 2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India.
  • 3. Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana 500 037, India.
  • 4. Formulation Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176 061, India.
PMID: 42080664 DOI: 10.1021/acs.jmedchem.6c00137
Abstract

To overcome the ever-growing global challenge of Antibiotic resistance, we have synthesized a series of 17 ciprofloxacin-lipophilic (CIP-LIP) conjugates using a carbodiimide reagent. The Antibacterial efficacy of these conjugates was evaluated in vitro against two Bacterial strains: Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (PAO1). Notably, three synthesized conjugates, 9, 19, and 21 (MIC = 0.06 μg/mL), exhibited 2-fold higher Antibacterial activity than CIP (MIC = 0.125 μg/mL) against S. aureus. Conjugate 11 emerged as the most potent against P. aeruginosa, with an MIC of 2 μg/mL. Additionally, conjugates 9 and 11 displayed significant antibiofilm activity against both P. aeruginosa and S. aureus. Compound 9 exhibited no cytotoxic effect against both HepG2 and J774A at concentrations of 100 μg/mL. Collectively, these findings open new avenues for the development of lipophilic-based CIP conjugates as modified ciprofloxacin derivatives for targeting Bacterial biofilms and DNA gyrase.

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